Cyclodextrin dimers and derivatives thereof, methods for preparing them and their use, in particular, for the solubilizing pharmacologically active substances

Abstract

The invention relates to a compound according to the following general formula (I), in which: m represents an integer equal to 5, 6 or 7; n and n 1 represent an integer from 1 to 5; the A groups represent, in particular, a hydrogenated atom; X represents O or S; Y represents, in particular, a group NR 1 , R 1 , representing, in particular, a hydrogenated atom; W represents CH or N; and Z represents, in particular, a hydrogenated atom.

1. An inclusion complex of a compound according to formula I with a pharmacologically active molecule, the molar ratio between the compound and the pharmacologically active molecule being approximately 10:1 to approximately 1:2, and said formula I being: 
       
         
           
           
               
               
           
         
       
       wherein,
 m represents an integer equal to 5, 6 or 7; 
 n and n′ represent an integer from 1 to 5, n and n′ being identical or different; 
 A represents a hydrogen atom, an acyl, an alkyl, a hydroxyalkyl or a sulphoalkyl group of 1 to 16 carbon atoms, each A being identical or different; 
 X represents O or S, 
 Y represents a group selected from the group consisting of: 
 (i) an —NR 1 — group, wherein R 1  represents a hydrogen atom or an alkyl group comprising from 1 to 6 carbon atoms, such that said compound corresponds to formula (I-a): 
 
       
         
           
           
               
               
           
         
         (ii) an amide group of formula —NH—CO—(CH 2 ) q —NR 1 —, wherein q represents an integer from 1 to 5 and R 1  represents a hydrogen atom or an alkyl group comprising from 1 to 6 carbon atoms, such that said compound corresponds to formula (I-b): 
       
       
         
           
           
               
               
           
         
         (iii) a cysteaminyl group of formula —S—(CH 2 ) r —NR 1 —, wherein r represents an integer from 2 to 5 and R 1  represents a hydrogen atom or an alkyl group comprising from 1 to 6 carbon atoms, so that said compound corresponds to formula (I-c): 
       
       
         
           
           
               
               
           
         
         W represents CH or N; and 
         Z represents a group selected from the group consisting of: 
         a carbamate substituent of formula 
       
       
         
           
           
               
               
           
         
         an amine substituent of formula 
       
       
         
           
           
               
               
           
         
         a quaternary ammonium group of formula 
       
       
         
           
           
               
               
           
         
         a urea or thiourea substituent of formula: 
       
       
         
           
           
               
               
           
         
         a group of formula 
       
       
         
           
           
               
               
           
         
         one of a group according to formula C(═O)OR 3 , a group according to formula C(═O)R 2 , and a group carrying the amine, ammonium quaternary urea or thiourea functionalities, of respective formulae: 
       
       
         
           
           
               
               
           
         
         p representing an integer from 0 to 5, when W represents CH, and from 2 to 5, when W represents N, 
         X′ representing O or S, 
         R 2  representing a hydrogen atom or an alkyl group comprising from 1 to 6 carbon atoms, 
         R 3  representing a substituent allowing the hydrolysis of the carbamate group in order to release the amine function, and 
         R representing one of: 
         (i) a substituent selected from the group consisting of a hydrogen atom, a linear or branched alkyl group of 1 to 12 carbon atom, an aromatic group , and an aromatic group carrying at least one substituent on the aromatic ring, said at least one substituent selected from the group consisting of methyl, ethyl, chlorine, bromine, iodine, nitro, hydroxyl, methoxyl and acetamido substituents, and 
         (ii) a biological recognition element selected from the group consisting of an amino acid, a peptide, a monosaccharide, an oligosaccharide, and a multiplication element with sevaral branchings, said branchings selected from the group consisting of:
 (a) glucide groups, which can be identical or different, and 
 (b) molecular structure allowing detection by fluorescent or radioactive visualization. 
 
       
     
     
       2. The inclusion complex according to  claim 1  wherein the pharmacologically active molecule is a ditopic molecule. 
     
     
       3. The inclusion complex according to  claim 1 , wherein the pharmacologically active molecule is an antineoplastic agent. 
     
     
       4. A pharmaceutical composition comprising the inclusion complex according to  claim 1 , in association with a pharmacologically acceptable vehicle. 
     
     
       5. A pharmaceutical composition comprising the inclusion complex according to  claim 1 , in association with a pharmacologically acceptable vehicle, in the form of aqueous solution. 
     
     
       6. A pharmaceutical composition comprising the inclusion complex according to  claim 1 , in association with a pharmacologically acceptable vehicle, wherein said complex is approximately 100 mg to approximately 750 mg per unit dose of said pharmaceutical composition.